title: Chromosomal imbalance letter: Phenotypic consequences of combined deletion 8pter and duplication 15qter.
abstract: Exact breakpoint determination by oligonucleotide array-CGH has improved the analysis of genotype-phenotype correlations in cases with chromosome aberrations allowing a more accurate definition of relevant genes, particularly their isolated or combined impact on the phenotype in an unbalanced state. Chromosomal imbalances have been identified as one of the major causes of mental retardation and/or malformation syndromes and they are observed in ~2-5% of the cases. Here we report a female child born to non-consanguineous parents and having multiple congenital anomalies such as atrial septal defect and multiple ventricular septal defects, convergent strabismus, micropthalmia, seizures and mental retardation, with her head circumference and stature normal for her age. Cytogenetic study suggested 46,XX,add(8)(p23). Further analysis by array-CGH using 44K oligonucleotide probe confirmed deletion on 8p23.3p23.1 of 7.1 Mb and duplication involving 15q23q26.3 of 30 Mb size leading to 46,XX,der(8)t(8;15)(p23.3;q23)pat.arr 8p23.3p23.1(191,530-7,303,237)x1,15q23q26.3(72,338,961-102,35,195)x3. The unique phenotypic presentation in our case may have resulted from either loss or gain of a series of contiguous genes which may have resulted in a direct phenotypic effect and/or caused a genetic regulatory disturbance. Double segmental aberrations may have conferred phenotypic variability, as in our case, making it difficult to predict the characteristics that evolved as a result of the global gene imbalance, caused by the concomitant deletion and duplication.
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Frenny
authors.initials: F
authors.lastname: Sheth
authors.affiliation: Laboratory of Medical Genetics, Jeanne de Flandre Hospital CHRU de Lille, Lille Cedex, France.
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Stuti
authors.initials: S
authors.lastname: Tewari
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, NE1 4EP, UK.
authors.forename: Harsh
authors.initials: H
authors.lastname: Sheth
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Pritti
authors.initials: P
authors.lastname: Kumari
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Nidhish
authors.initials: N
authors.lastname: Nanavaty
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Sheth
keywords: 15q23 duplication; 8p23 deletion; Chromosomal imbalance; GATA4; IGF1R; MCPH1